STRIVE (Sierra Leone Trial to Introduce a Vaccine Against Ebola)

NCT ID: NCT02378753

Last Updated: 2018-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 8651 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2016-12-05

Brief Summary

The 2014 outbreak of Ebola in West Africa is the largest in recorded history with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission. This study will accelerate introduction and use of monovalent recombinant vesicular stomatitis virus Ebola vaccine (rVSVΔG-ZEBOV) among healthcare workers and frontline personnel involved in the Ebola outbreak response in Sierra Leone, while concurrently evaluating the safety and efficacy of the vaccine.

This is an unblinded, randomized trial with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area.

Detailed Description

The Ebola outbreak was confirmed in March 2014 with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. While there are no U.S. Food and Drug Administration (FDA)-approved pharmaceuticals to prevent or treat Ebola, two candidate vaccines are being tested in humans for dosing, tolerability, and safety. This study will evaluate monovalent recombinant vesicular stomatitis virus Ebola vaccine that remains replication competent (rVSVΔG-ZEBOV) in Sierra Leone.

The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission.

This unblinded, randomized trial will evaluate vaccine efficacy (VE) and safety with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area. This includes: 1) personnel working in healthcare facilities where care is provided for Ebola patients; 2) personnel working in non-Ebola healthcare facilities who may have exposure to undiagnosed Ebola-infected individuals; and 3) personnel working in one of the following job categories: surveillance team, ambulance team, or laboratory worker responsible for swabbing deceased persons. Staff members involved in this study are also eligible to receive the vaccine under this protocol; study staff will be followed for 6 months post-vaccination to monitor for safety of rVSVΔG-ZEBOV.

Eligible participants within a healthcare facility or frontline team will be enrolled and individually randomized to either immediate or deferred vaccination. A single dose of rVSVΔG-ZEBOV will be administered intramuscularly. Immediate vaccination is defined as vaccination within 7 days of enrollment and deferred vaccination is defined as vaccination at the end of an 18-24 week follow-up period. Participants will not be blinded to the randomized assignment of immediate or deferred vaccination. All enrolled participants will have the opportunity to receive rVSVΔG-ZEBOV by the end of the study. Enrollment and vaccination will be phased over time.

Ebola events that occur during the 18-24 week post-enrollment will be included in the VE analysis, with the immediate vaccination arm contributing vaccinated follow-up time and the deferred vaccination arm contributing unvaccinated follow-up time. All participants, regardless of randomized assignment, will be followed for 6 months after vaccination to monitor for safety of rVSVΔG-ZEBOV.

Conditions

Hemorrhagic Fever, Ebola

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

rVSVΔG-ZEBOV (immediate vaccination)

One intramuscular (deltoid) injection of rVSVΔG-ZEBOV (2 x 10\^7 plaque forming units)

Group Type: EXPERIMENTAL

rVSVΔG-ZEBOV

Intervention Type: BIOLOGICAL

The rVSVΔG-ZEBOV vaccine is comprised of a single recombinant VSV isolate (11481 nontypeable) modified to replace the gene encoding the G envelope GP with the gene encoding the envelope GP from ZEBOV (Kikwit, 1995 strain).

rVSVΔG-ZEBOV (deferred vaccination)

One intramuscular (deltoid) injection of rVSVΔG-ZEBOV (2 x 10\^7 plaque forming units) in participants randomized to receive deferred vaccination (18-24 weeks after enrollment).

Group Type: EXPERIMENTAL

rVSVΔG-ZEBOV

Intervention Type: BIOLOGICAL

The rVSVΔG-ZEBOV vaccine is comprised of a single recombinant VSV isolate (11481 nontypeable) modified to replace the gene encoding the G envelope GP with the gene encoding the envelope GP from ZEBOV (Kikwit, 1995 strain).

Interventions

rVSVΔG-ZEBOV

The rVSVΔG-ZEBOV vaccine is comprised of a single recombinant VSV isolate (11481 nontypeable) modified to replace the gene encoding the G envelope GP with the gene encoding the envelope GP from ZEBOV (Kikwit, 1995 strain).

Intervention Type: BIOLOGICAL

Other Intervention Names

BPSC-1001

Eligibility Criteria

Inclusion Criteria

1. Age 18 years or older.

2. Member of target population at the time of enrollment:

• active worker in an Ebola care, holding, or treatment center (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
• active worker in a facility providing non-Ebola-related healthcare (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
• active frontline worker in one of the following job categories: surveillance team, ambulance team, burial worker, or worker responsible for swabbing deceased persons.

3. Reasonably anticipates living in Sierra Leone for the 18-24 weeks following enrollment.

4. Reachable by phone throughout the 6 month post-vaccination safety follow-up period.

5. Willing to adhere to personal protective equipment (PPE) and infection control recommendations.

6. Able and willing to complete the informed consent process and study procedures.

7. Willing to receive vaccine in either the immediate or the deferred trial arms, according to random assignment.

Exclusion Criteria

1. History of Ebola (self-report).

2. Prior receipt of experimental Ebola or Marburg vaccine.

3. History of human immunodeficiency virus (HIV) or clinically important immunodeficiency (self-report).

4. Any history of allergy or anaphylaxis to prior vaccines

5. Breast-feeding an infant or child.

6. Any reason the investigator suspects that data collected from this person would be incomplete or of poor quality.

7. Current pregnancy (a negative urine pregnancy test is required for women participants <50 years of age who self-report as not pregnant).

8. Currently being followed for known exposure to Ebola.

9. Known experimental research agents or other vaccine within 28 days (4 weeks) before vaccination.

10. Fever ≥ 38.0°C (100.4°F) at time of vaccination.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Sierra Leone

OTHER

Sponsor Role: collaborator

Ministry of Health and Sanitation, Sierra Leone

OTHER_GOV

Sponsor Role: collaborator

Department of Health and Human Services

FED

Sponsor Role: collaborator

eHealth Africa

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohamed Samai, MBChB,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sierra Leone

Locations

College of Medicine and Allied Health Sciences (COMAHS)

Freetown, Western Area Urban, Sierra Leone

Bombali

Bombali District, , Sierra Leone

Port Loko

Port Loko District, , Sierra Leone

Tonkolili

Tonkolili District, , Sierra Leone

Western Area Rural

Western Area District, , Sierra Leone

Countries

Sierra Leone

References

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Reference Type: DERIVED

PMID: 36208978 (View on PubMed)

Legardy-Williams JK, Carter RJ, Goldstein ST, Jarrett OD, Szefer E, Fombah AE, Tinker SC, Samai M, Mahon BE. Pregnancy Outcomes among Women Receiving rVSVDelta-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola. Emerg Infect Dis. 2020 Mar;26(3):541-548. doi: 10.3201/eid2603.191018. Epub 2020 Mar 17.

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Kabineh AK, Carr W, Motevalli M, Legardy-Williams J, Vincent W, Mahon BE, Samai M. Operationalizing International Regulatory Standards in a Limited-Resource Setting During an Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) Experience. J Infect Dis. 2018 May 18;217(suppl_1):S56-S59. doi: 10.1093/infdis/jiy111.

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PMID: 29788349 (View on PubMed)

Carter RJ, Senesi RGB, Dawson P, Gassama I, Kargbo SAS, Petrie CR, Rogers MH, Samai M, Luman ET. Participant Retention in a Randomized Clinical Trial in an Outbreak Setting: Lessons From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). J Infect Dis. 2018 May 18;217(suppl_1):S65-S74. doi: 10.1093/infdis/jiy094.

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Samai M, Seward JF, Goldstein ST, Mahon BE, Lisk DR, Widdowson MA, Jalloh MI, Schrag SJ, Idriss A, Carter RJ, Dawson P, Kargbo SAS, Leigh B, Bawoh M, Legardy-Williams J, Deen G, Carr W, Callis A, Lindblad R, Russell JBW, Petrie CR, Fombah AE, Kargbo B, McDonald W, Jarrett OD, Walker RE, Gargiullo P, Bash-Taqi D, Gibson L, Fofanah AB, Schuchat A; STRIVE Study Team. The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak. J Infect Dis. 2018 May 18;217(suppl_1):S6-S15. doi: 10.1093/infdis/jiy020.

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Callis A, Carter VM, Ramakrishnan A, Albert AP, Conteh L, Barrie AA, Fahnbulleh L, Koroma MM, Saidu S, Williams O, Samai M. Lessons Learned in Clinical Trial Communication During an Ebola Outbreak: The Implementation of STRIVE. J Infect Dis. 2018 May 18;217(suppl_1):S40-S47. doi: 10.1093/infdis/jix558.

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Jusu MO, Glauser G, Seward JF, Bawoh M, Tempel J, Friend M, Littlefield D, Lahai M, Jalloh HM, Sesay AB, Caulker AF, Samai M, Thomas V, Farrell N, Widdowson MA. Rapid Establishment of a Cold Chain Capacity of -60 degrees C or Colder for the STRIVE Ebola Vaccine Trial During the Ebola Outbreak in Sierra Leone. J Infect Dis. 2018 May 18;217(suppl_1):S48-S55. doi: 10.1093/infdis/jix336.

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Other Identifiers

CDC-NCIRD-6689

Identifier Type: -

Identifier Source: org_study_id